The proposed project is concerned with studies of defense mechanisms of lung cells against toxic partial pressures of oxygen as determined in an in vitro system. Alveolar macrophages from rats, rabbits, guinea pigs and humans will be maintained in vitro, and the influence of direct exposure to high oxygen tension on cellular adherence, cellular lactic dehydrogenase content and leakage into the medium, phagocytosis and bacterial "killing", and cellular metabolism will be characterized. Possible protective mechanisms against oxygen toxicity of these cells will be assessed by: 1) the addition of superoxide dismutase, peroxidase, and catalase; 2) the addition of hydroxyl radical scavengers such as mannitol; 3) the addition of quenchers of singlet oxygen such as carotenoids; 4) the blockage of xanthine oxidase with allopurinol; 5) the addition of antioxidants such as the tocopherols; and 6) the addition of antithyroid drugs. Cell-free lung washes from normal and oxygen toxic animals will be used to evaluate possible acceleration of oxygen toxicity or protection against oxygen toxicity of alveolar macrophages in vitro. Possible induction of protection against oxygen toxicity by previous exposure of macrophages to moderately elevated oxygen tensions in vitro will be assessed, and the possible induction of superoxide dismutase, peroxidase, and catalase by elevated oxygen tensions will be evaluated. The influence of phagocytosis on the oxygen toxicity of the macrophage will be evaluated. Possible protective mechanisms against oxygen toxicity as determined by in vitro studies will be assessed further in the intact animal maintained in chambers with controlled environmental gas composition.